Glaucoma is one of the three leading causes of blindness in the United States and it is a leading cause of blindness in the world. Over 2.2 million people in the United States have glaucoma, and several million more are at risk of developing the disease. As the population ages, the number of individuals with glaucoma will continue to grow since glaucoma affects the oldest individuals disproportionately.
Glaucoma is not just one disease, rather, it is a spectrum of conditions that share a final common pathway of acquired, progressive deterioration of the neuronal components of the optic nerve. Neuronal death results in loss of vision once a sufficient number of individual nerves are destroyed.
Factors associated with the development of glaucoma and its progression have been identified and are in the process of being clarified. Elevated intraocular pressure (IOP) is the leading cause of glaucoma. Pressure is elevated because drainage of aqueous fluid from within the eye is impaired. Current treatments for glaucoma center on reducing pressure in the eye by reducing the amount of aqueous fluid being produced or by enhancing the flow of fluid out of the eye by mechanical or other means. Currently available drugs do not enhance or restore functioning of the natural drainage pathway.
Glaucoma patients may also suffer reduced blood flow to the optic nerve and neuronal tissue, diminished resistance of the nerve tissue to damage, and compliance of connective tissue surrounding and supporting the optic nerve. Current treatments do not address any such factors. Only one agent, Memantine, is in phase III clinical trials (Allergan) as an agent that may increase the relative resistance of the nerve tissue to damage (i.e., neuroprotective).
The use of statins has been associated in some studies with a diminished risk of developing age-related macular degeneration as well as a potential for reducing the risk for several medical conditions related to cardiovascular disease (Hall et al, BMJ 323:375-376 (2001), McCarty et al, MJA 175:340 (2001), Shovman et al, Immunol. Res. 25:271-285 (2002), Kagansky et al, QJM 94:457-463 (2001)). The presumed direct causal mechanisms have centered on the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in reducing cholesterol production and enhancing LDL-cholesterol removal from plasma. To the extent that excess total cholesterol or LDL cholesterol is implicated in these conditions, use of the statins would reduce the risk of developing, or at least delay the onset of, these conditions. Statins also inhibit non-steroidal isoprenoid production (Edwards and Ericsson, Annu. Rev. Biochem. 68:157-185 (1999), Comparato et al, Nutr. Metab. Cardiovasc. Dis. 11:328-343 (2001), Takemoto and Liao, Arterioscler. Throm. Vasc. Biol. 21:1712-1719 (2001)). Many statins also inhibit the activity of rho-kinase, such inhibition has been shown to enhance aqueous outflow (Rao et al, Invest. Ophthalmol. & Vis. Sci. 42:1029-1037 (2001)). There may, of course, be as yet undiscovered or indirect effects of these compounds that would help explain their protective associations.
The present invention provides a new approach to the field of therapeutics for patients with glaucoma. Provided is a method of preventing or treating glaucoma using statins.